Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma

Seiichi Yano, Kenji Ashida, Hiromi Nagata, Kenji Ohe, Naoko Wada, Yukina Takeichi, Yuki Hanada, Yuta Ibayashi, Lixiang Wang, Shohei Sakamoto, Ryuichi Sakamoto, Uchi Hiroshi, Motoaki Shiratsuchi, Masutaka Furue, Masatoshi Nomura, Yoshihiro Ogawa

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Abstract

Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85years; 54% female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P<0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

Original languageEnglish
Article number36
JournalBMC Endocrine Disorders
Volume18
Issue number1
DOIs
Publication statusPublished - Jun 8 2018

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Melanoma
Thyroid Gland
Antibodies
Thyrotoxicosis
Hypothyroidism
nivolumab
Peroxidase
Thyroxine
Cell Death
Monoclonal Antibodies
Survival

All Science Journal Classification (ASJC) codes

  • Endocrinology, Diabetes and Metabolism

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Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma. / Yano, Seiichi; Ashida, Kenji; Nagata, Hiromi; Ohe, Kenji; Wada, Naoko; Takeichi, Yukina; Hanada, Yuki; Ibayashi, Yuta; Wang, Lixiang; Sakamoto, Shohei; Sakamoto, Ryuichi; Hiroshi, Uchi; Shiratsuchi, Motoaki; Furue, Masutaka; Nomura, Masatoshi; Ogawa, Yoshihiro.

In: BMC Endocrine Disorders, Vol. 18, No. 1, 36, 08.06.2018.

Research output: Contribution to journalArticle

Yano, Seiichi ; Ashida, Kenji ; Nagata, Hiromi ; Ohe, Kenji ; Wada, Naoko ; Takeichi, Yukina ; Hanada, Yuki ; Ibayashi, Yuta ; Wang, Lixiang ; Sakamoto, Shohei ; Sakamoto, Ryuichi ; Hiroshi, Uchi ; Shiratsuchi, Motoaki ; Furue, Masutaka ; Nomura, Masatoshi ; Ogawa, Yoshihiro. / Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma. In: BMC Endocrine Disorders. 2018 ; Vol. 18, No. 1.
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abstract = "Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85years; 54{\%} female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29{\%}). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P<0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.",
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T1 - Nivolumab-induced thyroid dysfunction lacking antithyroid antibody is frequently evoked in Japanese patients with malignant melanoma

AU - Yano, Seiichi

AU - Ashida, Kenji

AU - Nagata, Hiromi

AU - Ohe, Kenji

AU - Wada, Naoko

AU - Takeichi, Yukina

AU - Hanada, Yuki

AU - Ibayashi, Yuta

AU - Wang, Lixiang

AU - Sakamoto, Shohei

AU - Sakamoto, Ryuichi

AU - Hiroshi, Uchi

AU - Shiratsuchi, Motoaki

AU - Furue, Masutaka

AU - Nomura, Masatoshi

AU - Ogawa, Yoshihiro

PY - 2018/6/8

Y1 - 2018/6/8

N2 - Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85years; 54% female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P<0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

AB - Background: Nivolumab, an anti-programmed cell death-1 monoclonal antibody, has improved the survival of patients with malignant melanoma. Despite its efficacy, nivolumab inconsistently induces thyroid dysfunction as an immune-related adverse event (irAE). This study aimed to evaluate nivolumab-induced thyroid dysfunction to determine the risks and mechanisms of thyroid irAEs. Methods: After excluding 10 patients, data of 24 patients with malignant melanoma (aged 17-85years; 54% female) were retrospectively analyzed. Results: Thyroid irAEs were observed in seven patients (29%). Three patients had hypothyroidism after preceding transient thyrotoxicosis, and the other four patients had hypothyroidism without thyrotoxicosis. Levothyroxine-Na replacement was required in three patients. Antithyroid antibody (ATA) titer was elevated in one of four assessable patients. The average (±SD) time to onset of thyroid irAE was 33.6 (±21.9) weeks. The administration period of nivolumab was longer in patients with thyroid irAEs than in those without thyroid irAEs (P<0.01). There were no significant differences between patients with and without thyroid irAEs regarding age, sex, tumor stage, response to nivolumab therapy, baseline thyroid function, antithyroid peroxidase antibody (anti-TPO Ab) and antithyroglobulin antibody (anti-Tg Ab). Conclusions: Thyroid dysfunction was a common irAE of nivolumab in malignant melanoma. Neither anti-TPO Ab nor anti-Tg Ab was associated with the risk for nivolumab-induced thyroid dysfunction. A conventional ATA-independent mechanism might be involved in thyroid irAEs. Further studies are required to clarify the mechanism and identify the predictive factors of thyroid irAEs.

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